Synthesis of 11 C-labeled ubiquinone and ubiquinol via Pd 0 -mediated rapid C-[ 11 C]methylation using [ 11 C]methyl iodide and 39-demethyl-39-(pinacolboryl)ubiquinone

Abstract

To enable positron emission tomography (PET) imaging of the in vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q 10 , their 11 C-radiolabeled counterparts were synthesized herein. 11 C-Labeled ubiquinone [ 11 C]-1 was realized by Pd-mediated rapid C-[ 11 C]methylation of [ 11 C]CH 3 I with 39-demethyl-39-(pinacolboryl)ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [ 11 C]-1 using Na 2 S 2 O 4 yielded 11 C-labeled ubiquinol [ 11 C]-2. The synthesis time and [ 11 C]CH 3 I-based radiochemical yield of [ 11 C]-1 were within 36 minutes and up to 53%, while those of [ 11 C]-2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [ 11 C]-1 and [ 11 C]-2 were confirmed to be applicable for animal PET studies. The analytical values of [ 11 C]-1 and [ 11 C]-2 are as follows: radioactivity of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/μmol, radiochemical purity of greater than 99% and greater than 95%, and chemical purity of greater than 99% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to 11 C-radiolabeled ubiquinone and ubiquinol via a pinacolborane-substituted ubiquinone derivative. Each PET probe was used for molecular imaging using rats to investigate the in vivo kinetics and biodistribution of the coenzyme Q 10 .